The invention of new catalytic methods for chemical synthesis of small organic molecules is a critical objective in modern organic chemistry because it is essential for the efficient manufacture of pharmaceutical agents. One class of reactions that has proven to be of significant utility is metal-catalyzed cross-couplings. These reactions are primarily used for the construction of Csp2-Csp2 bonds. Despite progress, however, cross-coupling of secondary and tertiary Csp3-based nucleophiles is still challenging. Furthermore, stereoselective variants of these processes are even more rare and present even greater obstacles. The studies described in this application seek to provide innovative solutions to these problems through the introduction of cross-coupling reactions that utilize Csp3-nucleophiles catalytically generated in situ from simple alkenes. Our rationale for development of these reactions is that readily available starting materials (alkenes, diboron reagents and organohalides) will be converted to synthetically versatile products that can be easily manipulated to a variety of biologically significant molecules. Preliminary data gathered in our lab are extremely encouraging for success in our proposed studies. In the first part of our program we will introduce methods for Pd-catalyzed cross-coupling of organohalides with nucleophilic Csp3-Cu-complexes generated in situ by migratory insertion of CuBpin complexes across alkenes. These reactions will provide uniquely efficient and modular approaches to compounds that readily map onto a variety of known biologically relevant molecules. In the second phase of our studies, stereoselective (both diastereoselective and enantioselective) variants of these reactions will be developed. Such processes will allow for up to three new stereogenic centers to be generated in a single operation. Finally, this exercise in reaction development will introduce new concepts and strategies in chemical synthesis by exploring new cross-coupling paradigms.